T‑Cells from HLA-B57:01+ Human Subjects Are Activated with Abacavir through Two Independent Pathways and Induce Cell Death by Multiple Mechanisms

• Published in: Chemical research in toxicology Vol. 26; no. 5; pp. 759 - 766
• Main Authors: Bell, Catherine C, Faulkner, Lee, Martinsson, Klara, Farrell, John, Alfirevic, Ana, Tugwood, Jonathan, Pirmohamed, Munir, Naisbitt, Dean J, Park, B. Kevin
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 20.05.2013
• Subjects: CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Cell Death - drug effects; Cell Line; Cell Proliferation; Clone Cells - cytology; Clone Cells - drug effects; Clone Cells - immunology; Cytokines - immunology; Dideoxynucleosides - chemistry; Dideoxynucleosides - pharmacology; Dose-Response Relationship, Drug; HLA-B Antigens - immunology; Humans; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - immunology; Lymphocyte Activation - drug effects; Structure-Activity Relationship

Susceptibility to abacavir hypersensitivity has been attributed to possession of the specific human leukocyte antigen allele HLA-B*57:01. HLA-B*57:01-restricted activation of CD8+ T-cells provides a link between the genetic association and the iatrogenic disease. The objectives of this study were to...